Clinical Trials /

Safety and Pharmacokinetics Study of MK-5890 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Adults With Advanced Solid Tumors (MK-5890-001)

NCT03396445

Description:

The purpose of this study is to assess the safety and pharmacokinetics of MK-5890 when administered alone and in combination with pembrolizumab (MK-3475) in adults with advanced solid tumors. The initial course of MK-5890 monotherapy or MK-5890 plus pembrolizumab combination therapy will be for up to 35 administrations (approximately 2 years). The safety and pharmacokinetics of MK-5890 when administered with pembrolizumab, pemetrexed and carboplatin will also be assessed in adults with non-squamous non-small cell lung cancer (NSCLC).

Related Conditions:
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Safety and Pharmacokinetics Study of MK-5890 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Adults With Advanced Solid Tumors (MK-5890-001)
  • Official Title: A Phase 1 Study of MK-5890 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 5890-001
  • SECONDARY ID: MK-5890-001
  • NCT ID: NCT03396445

Conditions

  • Pharmacokinetics
  • Solid Tumor

Interventions

DrugSynonymsArms
MK-5890Arm 1: MK-5890
PembrolizumabMK-3475Arm 2: MK-5890 + Pembrolizumab
PemetrexedALIMTA®Arm 3: MK-5890 + Pembrolizumab + Pemetrexed + Carboplatin
CarboplatinPARAPLATIN®Arm 3: MK-5890 + Pembrolizumab + Pemetrexed + Carboplatin

Purpose

The purpose of this study is to assess the safety and pharmacokinetics of MK-5890 when administered alone and in combination with pembrolizumab (MK-3475) in adults with advanced solid tumors. The initial course of MK-5890 monotherapy or MK-5890 plus pembrolizumab combination therapy will be for up to 35 administrations (approximately 2 years). The safety and pharmacokinetics of MK-5890 when administered with pembrolizumab, pemetrexed and carboplatin will also be assessed in adults with non-squamous non-small cell lung cancer (NSCLC).

Detailed Description

      Participants receiving MK-5890 monotherapy who experience disease progression may be eligible
      to switch to receiving MK-5890 plus pembrolizumab combination therapy for up to 35 cycles
      (approximately 2 years) at the discretion of the Investigator and approval of the Sponsor.
    

Trial Arms

NameTypeDescriptionInterventions
Arm 1: MK-5890ExperimentalParticipants receive escalating doses of MK-5890 via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
  • MK-5890
Arm 2: MK-5890 + PembrolizumabExperimentalParticipants receive escalating doses of MK-5890 via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
  • MK-5890
  • Pembrolizumab
Arm 3: MK-5890 + Pembrolizumab + Pemetrexed + CarboplatinExperimentalParticipants receive MK-5890 at the selected dose via IV infusion PLUS pembrolizumab 200 mg via IV infusion PLUS pemetrexed 500 mg/m^2 via IV infusion PLUS carboplatin Area Under the Curve (AUC) 5 mg/mL/min via IV infusion, all given on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
  • Pemetrexed
  • Carboplatin

Eligibility Criteria

        Inclusion Criteria:

          -  Arms 1 & 2: Histologically or cytologically confirmed advanced/metastatic solid tumor
             by pathology report and has received or been intolerant to all treatment known to
             confer clinical benefit.

          -  Arm 3: Histologically or cytologically confirmed diagnosis of stage IV (M1a or M1b per
             current American Joint Committee on Cancer criteria) non-squamous NSCLC.

          -  Measureable disease by RECIST 1.1. as assessed by the local site
             investigator/radiologist. Target lesions situated in a previously irradiated area are
             considered measurable if progression has been demonstrated in such lesions.

          -  Adequate organ function.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          -  Male participants must agree to use adequate contraception during the treatment period
             and for at least 120 days after the last dose of MK-5890 or pembrolizumab OR 180 days
             after the last dose of chemotherapeutic agents and refrain from donating sperm during
             this period.

          -  Female participants must not be pregnant or breast feeding and agree to follow use
             adequate contraception during the treatment period and for at least 120 days after the
             last dose of MK-5890 or pembrolizumab OR 180 days after the last dose of
             chemotherapeutic agents.

          -  Submit an evaluable baseline tumor sample for analysis (either a newly obtained or
             archival tumor sample).

        Exclusion Criteria:

          -  History of a second malignancy, unless potentially curative treatment has been
             completed with no evidence of malignancy for 2 years.

          -  Clinically active central nervous system metastases and/or carcinomatous meningitis.

          -  Has had a severe hypersensitivity reaction to treatment with a monoclonal antibody
             (mAb) and/or other components of the study treatment.

          -  Active infection requiring systemic treatment.

          -  History of interstitial lung disease.

          -  History of (noninfectious) pneumonitis that required steroids or current pneumonitis.

          -  Symptomatic ascites or pleural effusion.

          -  Previously had a stem cell or bone marrow transplant.

          -  Previously had a solid organ transplant.

          -  Active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive
             drugs) except vitiligo or resolved childhood asthma/atopy.

          -  Known human immunodeficiency virus (HIV) and/or active and acute Hepatitis B or C
             infections.

          -  Not fully recovered from any effects of major surgery without significant detectable
             infection.

          -  Pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the study.

          -  Had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2
             weeks for palliative radiation) before the first dose of study treatment, or has not
             recovered to Grade ≤1 or better from any AEs that were due to cancer therapeutics
             administered more than 4 weeks earlier.

          -  Expected to require any other form of antineoplastic therapy while participating in
             this study.

          -  On chronic systemic steroid therapy in excess of replacement doses (e.g., exceeding 10
             mg/day of prednisone equivalent), or on any other form of immunosuppressive
             medication.

          -  Regular user (including "recreational use") of any illicit drugs at the time of
             signing informed consent, or has a recent history (within the last year) of substance
             abuse (including alcohol), as determined by the treating investigator. Participants
             who use cannabis for medicinal purposes or to treat specific symptoms will not be
             excluded unless it is being abused in the opinion of the treating investigator.

          -  Received a live-virus vaccine within 28 days before the first dose of study treatment.

          -  Currently participating and receiving study treatment in a study of an investigational
             agent or has participated and received study treatment in a study of an
             investigational agent or has used an investigational device within 28 days before the
             first dose of study treatment.

        Additional Exclusion Criteria for Participants in Arm 3:

          -  Has received radiation therapy to the lung that is >30 Gray (Gy) within 6 months
             before the first dose of study treatment.

          -  Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs),
             other than an aspirin dose ≤1.3 g per day, for a 5-day period (8-day period for
             long-acting agents, such as piroxicam).

          -  Is unable or unwilling to take folic acid or vitamin B12 supplementation.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Arms 1 and 2: Dose-limiting Toxicities (DLTs) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 or Later
Time Frame:Cycle 1 (Up to 21 days)
Safety Issue:
Description:A DLT is defined as any of the following toxicities, if assessed by the investigator to be related to study treatment: Grade 4 nonhematologic toxicity; Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia; Grade 4 thrombocytopenia; Grade 3 thrombocytopenia associated with bleeding that requires a platelet transfusion; Nonhematologic adverse event (AE) Grade ≥3 in severity, with exceptions; Grade 3 or 4 nonhematologic laboratory abnormality if: clinically significant medical intervention is required or if abnormality leads to hospitalization, persists for >1 week or results in drug-induced liver injury with exceptions; Grade 3 or Grade 4 febrile neutropenia; Prolonged delay (>2 weeks) in initiating Cycle 2 due to treatment-related toxicity; Treatment-related toxicity resulting in participant study treatment discontinuation during Cycle 1; Missing >25% of the MK-5890 dose during Cycle 1 resulting from treatment-related AE; Grade 5 toxicity.

Secondary Outcome Measures

Measure:All Arms: Area Under the Concentration-Time Curve (AUC) of MK-5890
Time Frame:At designated time points (Up to 25 months)
Safety Issue:
Description:Blood samples will be obtained at designated time points for the assessment of MK-5890 AUC: Cycles 1-4: Day 1: Predose, (end of pembrolizumab infusion for participants receiving pembrolizumab), end of MK-5890 infusion, 2 hours post start of MK-5890 infusion, Days 2, 3, 5, 8 & 15: Once daily; Cycles 5, 6 & every 4 cycles thereafter: Day1: Predose; 30 days post last dose. Each cycle is 21 days. (Up to 25 months)
Measure:All Arms: Minimum Serum Concentration (Cmin) of MK-5890
Time Frame:At designated time points (Up to 25 months)
Safety Issue:
Description:Blood samples will be obtained at designated time points for the assessment of MK-5890 Cmin: Cycles 1-4: Day 1: Predose, (end of pembrolizumab infusion for participants receiving pembrolizumab), end of MK-5890 infusion, 2 hours post start of MK-5890 infusion, Days 2, 3, 5, 8 & 15: Once daily; Cycles 5, 6 & every 4 cycles thereafter: Day1: Predose; 30 days post last dose. Each cycle is 21 days. (Up to 25 months)
Measure:All Arms: Maximum Serum Concentration (Cmax) of MK-5890
Time Frame:At designated time points (Up to 25 months)
Safety Issue:
Description:Blood samples will be obtained at designated time points for the assessment of MK-5890 Cmax: Cycles 1-4: Day 1: Predose, (end of pembrolizumab infusion for participants receiving pembrolizumab), end of MK-5890 infusion, 2 hours post start of MK-5890 infusion, Days 2, 3, 5, 8 & 15: Once daily; Cycles 5, 6 & every 4 cycles thereafter: Day1: Predose; 30 days post last dose. Each cycle is 21 days. (Up to 25 months)
Measure:Arms 1 and 2: Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Time Frame:Up to 24 months
Safety Issue:
Description:The ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The ORR of MK-5890 when used as monotherapy and in combination with pembrolizumab (Arms 1 and 2) as assessed by the investigator will be presented.
Measure:Arm 3: Dose-limiting Toxicities (DLTs) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 or Later
Time Frame:Cycle 1 (Up to 21 days)
Safety Issue:
Description:A DLT is defined as any of the following toxicities, if assessed by the investigator to be related to study treatment: Grade 4 nonhematologic toxicity; Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia; Grade 4 thrombocytopenia; Grade 3 thrombocytopenia associated with bleeding that requires a platelet transfusion; Nonhematologic adverse event (AE) Grade ≥3 in severity, with exceptions; Grade 3 or 4 nonhematologic laboratory abnormality if: clinically significant medical intervention is required or if abnormality leads to hospitalization, persists for >1 week or results in drug-induced liver injury with exceptions; Grade 3 or Grade 4 febrile neutropenia; Prolonged delay (>2 weeks) in initiating Cycle 2 due to treatment-related toxicity; Treatment-related toxicity resulting in participant study treatment discontinuation during Cycle 1; Missing >25% of the MK-5890 dose during Cycle 1 resulting from treatment-related AE; Grade 5 toxicity.
Measure:Arm 3: Number of Participants with Adverse Events (AEs)
Time Frame:Up to 27 months
Safety Issue:
Description:An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants in Arm 3 who experience at least one AE will be presented.
Measure:Arm 3: Number of Study Treatment Discontinuations Due to an Adverse Event (AE)
Time Frame:Up to 24 months
Safety Issue:
Description:The number of participants in Arm 3 who discontinue study treatment due to an AE will be presented.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Last Updated